Low back pain and osteoarthritis pain: a perspective of estrogen

Huiwen Pang , Shihui Chen , David M. Klyne , David Harrich , Wenyuan Ding , Sidong Yang , Felicity Y. Han

Bone Research ›› 2023, Vol. 11 ›› Issue (1) : 42

PDF
Bone Research ›› 2023, Vol. 11 ›› Issue (1) : 42 DOI: 10.1038/s41413-023-00280-x
Review Article

Low back pain and osteoarthritis pain: a perspective of estrogen

Author information +
History +
PDF

Abstract

Low back pain (LBP) is the world’s leading cause of disability and is increasing in prevalence more rapidly than any other pain condition. Intervertebral disc (IVD) degeneration and facet joint osteoarthritis (FJOA) are two common causes of LBP, and both occur more frequently in elderly women than in other populations. Moreover, osteoarthritis (OA) and OA pain, regardless of the joint, are experienced by up to twice as many women as men, and this difference is amplified during menopause. Changes in estrogen may be an important contributor to these pain states. Receptors for estrogen have been found within IVD tissue and nearby joints, highlighting the potential roles of estrogen within and surrounding the IVDs and joints. In addition, estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression, indicating its potential use as a therapeutic agent for people with LBP and OA pain. This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings. The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.

Cite this article

Download citation ▾
Huiwen Pang, Shihui Chen, David M. Klyne, David Harrich, Wenyuan Ding, Sidong Yang, Felicity Y. Han. Low back pain and osteoarthritis pain: a perspective of estrogen. Bone Research, 2023, 11(1): 42 DOI:10.1038/s41413-023-00280-x

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Nicolson PJA et al. Interventions to increase adherence to therapeutic exercise in older adults with low back pain and/or hip/knee osteoarthritis: a systematic review and meta-analysis. Br. J. Sports Med., 2017, 51: 791-799

[2]

Fatoye F, Gebrye T, Odeyemi I. Real-world incidence and prevalence of low back pain using routinely collected data. Rheumatol. Int., 2019, 39: 619-626

[3]

Will JS, Bury DC, Miller JA. Mechanical low back pain. Am. Fam. Physician, 2018, 98: 421-428

[4]

Jiang JW et al. Up-regulation of TRAF2 inhibits chondrocytes apoptosis in lumbar facet joint osteoarthritis. Biochem. Biophys. Res. Co., 2018, 503: 1659-1665

[5]

Diwan AD, Melrose J. Intervertebral disc degeneration and how it leads to low back pain. JOR Spine, 2023, 6: e1231

[6]

Hoy D et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum., 2012, 64: 2028-2037

[7]

Hunter DJ, McDougall JJ, Keefe FJ. The symptoms of osteoarthritis and the genesis of pain. Rheum. Dis. Clin. North Am., 2008, 34: 623-643

[8]

Wu A et al. Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Ann. Transl. Med., 2020, 8: 299

[9]

Wáng YX, Wáng JQ, Káplár Z. Increased low back pain prevalence in females than in males after menopause age: evidences based on synthetic literature review. Quant. Imaging Med. Surg., 2016, 6: 199

[10]

Dulay GS, Cooper C, Dennison EM. Knee pain, knee injury, knee osteoarthritis & work. Best. Pr. Res. Clin. Rheumatol., 2015, 29: 454-461

[11]

Chidi-Ogbolu N, Baar K. Effect of estrogen on musculoskeletal performance and injury risk. Front. Physiol., 2018, 9: 1834

[12]

Richardson H et al. Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial. Menopause, 2020, 27: 693-700

[13]

Dedicação AC et al. Prevalence of musculoskeletal pain in climacteric women of a Basic Health Unit in São Paulo/SP. Rev. dor, 2017, 18: 212-216

[14]

Gibson CJ, Li Y, Bertenthal D, Huang AJ, Seal KH. Menopause symptoms and chronic pain in a national sample of midlife women veterans. Menopause, 2019, 26: 708-713

[15]

Klyne DM et al. Cohort profile: why do people keep hurting their back? BMC Res. Notes, 2020, 13

[16]

Klyne DM, Barbe MF, James G, Hodges PW. Does the interaction between local and systemic inflammation provide a link from psychology and lifestyle to tissue health in musculoskeletal conditions? Int. J. Mol. Sci., 2021, 22: 7299

[17]

Vergroesen PPA et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthr. Cartil., 2015, 23: 1057-1070

[18]

Millecamps M, Stone LS. Delayed onset of persistent discogenic axial and radiating pain after a single-level lumbar intervertebral disc injury in mice. Pain, 2018, 159: 1843-1855

[19]

Erwin WM, Hood KE. The cellular and molecular biology of the intervertebral disc: a clinician’s primer. J. Can. Chiropr. Assoc., 2014, 58: 246-257

[20]

Ghannam M et al. Surgical anatomy, radiological features, and molecular biology of the lumbar intervertebral discs. Clin. Anat., 2017, 30: 251-266

[21]

De Geer CM. Intervertebral disk nutrients and transport mechanisms in relation to disk degeneration: a narrative literature review. J. Chiropr. Med., 2018, 17: 97-105

[22]

Kim JH, Ham CH, Kwon WK. Current knowledge and future therapeutic prospects in symptomatic intervertebral disc degeneration. Yonsei Med. J., 2022, 63: 199-210

[23]

Oichi T, Taniguchi Y, Oshima Y, Tanaka S, Saito T. Pathomechanism of intervertebral disc degeneration. JOR Spine, 2020, 3: e1076

[24]

Gruber HE, Hanley EN. Analysis of aging and degeneration of the human intervertebral disc-Comparison of surgical specimens with normal controls. Spine, 1998, 23: 751-757

[25]

Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse? Science, 2003, 299: 1355-1359

[26]

Sadowska A et al. Inflammaging in cervical and lumbar degenerated intervertebral discs: analysis of proinflammatory cytokine and TRP channel expression. Eur. Spine J., 2018, 27: 564-577

[27]

latridis JC, Godburn K, Wuertz K, Alini M, Roughley PJ. Region-dependent aggrecan degradation patterns in the rat intervertebral disc are affected by mechanical loading in vivo. Spine, 2011, 36: 203-209

[28]

Gellhorn AC, Katz JN, Suri P. Osteoarthritis of the spine: the facet joints. Nat. Rev. Rheumatol., 2013, 9: 216-224

[29]

Suri P, Hunter DJ, Rainville J, Guermazi A, Katz JN. Presence and extent of severe facet joint osteoarthritis are associated with back pain in older adults. Osteoarthr. Cartil., 2013, 21: 1199-1206

[30]

Morris M, Pellow J, Solomon EM, Tsele-Tebakang T. Physiotherapy and a homeopathic complex for chronic low-back pain due to osteoarthritis: a randomized, controlled pilot study. Alter. Ther. Health Med., 2016, 22: 48-56

[31]

Lindsey, T. & Dydyk, A. M. in StatPearls (2023).

[32]

O’Leary SA et al. Facet joints of the spine: structure-function relationships, problems and treatments, and the potential for regeneration. Annu. Rev. Biomed. Eng., 2018, 20: 145-170

[33]

Caelers IJ et al. Lumbar intervertebral motion analysis during flexion and extension cinematographic recordings in healthy male participants: protocol. JMIR Res. Protoc., 2020, 9: e14741

[34]

Vina ER, Kwoh CK. Epidemiology of osteoarthritis: literature update. Curr. Opin. Rheumatol., 2018, 30: 160-167

[35]

Glyn-Jones S et al. Osteoarthritis. Lancet, 2015, 386: 376-387

[36]

Chen D et al. Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res., 2017, 5: 16044

[37]

Alpay-Kanitez N, Celik S, Bes C. Polyarthritis and its differential diagnosis. Eur. J. Rheumatol., 2019, 6: 167-173

[38]

Prieto-Alhambra D et al. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis: influences of age, gender and osteoarthritis affecting other joints. Ann. Rheum. Dis., 2014, 73: 1659-1664

[39]

Murphy LB et al. One in four people may develop symptomatic hip osteoarthritis in his or her lifetime. Osteoarthr. Cartil., 2010, 18: 1372-1379

[40]

Losina E et al. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res., 2013, 65: 703-711

[41]

Glass N et al. Examining sex differences in knee pain: the multicenter osteoarthritis study. Osteoarthr. Cartil., 2014, 22: 1100-1106

[42]

Belachew EB, Sewasew DT. Molecular mechanisms of endocrine resistance in estrogen-positive breast cancer. Front. Endocrinol., 2021, 12: 599586

[43]

Cauley JA. Estrogen and bone health in men and women. Steroids, 2015, 99: 11-15

[44]

Nilsson S, Gustafsson . Estrogen receptors: therapies targeted to receptor subtypes. Clin. Pharm. Ther., 2011, 89: 44-55

[45]

Pöllänen E et al. Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre‐ and postmenopausal women. Aging Cell, 2011, 10: 650-660

[46]

Ali ES, Mangold C, Peiris AN. Estriol: emerging clinical benefits. Menopause, 2017, 24: 1081-1085

[47]

Kumar RS, Goyal N. Estrogens as regulator of hematopoietic stem cell, immune cells and bone biology. Life Sci., 2021, 269: 119091

[48]

Emmanuelle NE et al. Critical role of estrogens on bone homeostasis in both male and female: from physiology to medical implications. Int. J. Mol. Sci., 2021, 22: 1568

[49]

Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol. Metab., 2012, 23: 576-581

[50]

Levin ER. Extranuclear steroid receptors are essential for steroid hormone actions. Annu. Rev. Med., 2015, 66: 271-280

[51]

Roman-Blas JA, Castaneda S, Largo R, Herrero-Beaumont G. Osteoarthritis associated with estrogen deficiency. Arthritis Res. Ther., 2009, 11: 241

[52]

Song XX et al. Estrogen receptor expression in lumbar intervertebral disc of the elderly: gender- and degeneration degree-related variations. Jt. Bone Spine, 2014, 81: 250-253

[53]

Song XX, Shi S, Guo Z, Li XF, Yu BW. Estrogen receptors involvement in intervertebral discogenic pain of the elderly women: Colocalization and correlation with the expression of Substance P in nucleus pulposus. Oncotarget, 2017, 8: 38136-38144

[54]

Wei AQ et al. Expression and functional roles of estrogen receptor GPR30 in human intervertebral disc. J. Steroid Biochem., 2016, 158: 46-55

[55]

Dreier R, Ising T, Ramroth M, Rellmann Y. Estradiol inhibits ER stress-induced apoptosis in chondrocytes and contributes to a reduced osteoarthritic cartilage degeneration in female mice. Front. Cell Dev. Biol., 2022, 10: 913118

[56]

Braidman IP et al. Localization of estrogen receptor β protein expression in adult human bone. J. Bone Min. Res., 2001, 16: 214-220

[57]

Dietrich W et al. Estrogen Receptor-β Is the Predominant Estrogen Receptor Subtype in Normal Human Synovia. J. Soc. Gynecol. Investig., 2006, 13: 512-517

[58]

Hang X et al. Estrogen Protects Articular Cartilage by Downregulating ASIC1a in Rheumatoid Arthritis. J. Inflamm. Res., 2021, 14: 843-858

[59]

Maneix L et al. 17Beta-oestradiol up-regulates the expression of a functional UDP-glucose dehydrogenase in articular chondrocytes: comparison with effects of cytokines and growth factors. Rheumatology., 2008, 47: 281-288

[60]

Claassen H, Schünke M, Kurz B. Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage. Cell Tissue Res., 2005, 319: 439-445

[61]

Christgau S et al. Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM). Menopause, 2004, 11: 508-518

[62]

Oestergaard S et al. Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation. Arthritis Rheum., 2006, 54: 2441-2451

[63]

SILBERBERG M, SILBERBERG R. Modifying action of estrogen on the evolution of osteoarthrosis in mice of different ages. Endocrinology, 1963, 72: 449-451

[64]

Tsai CL, Liu TK. Estradiol-induced knee osteoarthrosis in ovariectomized rabbits. Clin. Orthop. Relat. Res., 1993, 291: 295-302

[65]

Rosner IA et al. Pathologic and metabolic responses of experimental osteoarthritis to estradiol and an estradiol antagonist. Clin. Orthop. Relat. Res., 1982, 171: 280-286

[66]

Ha KY et al. Expression of estrogen receptor of the facet joints in degenerative spondylolisthesis. Spine, 2005, 30: 562-566

[67]

Wang T, Zhang L, Huang C, Cheng AG, Dang GT. Relationship between osteopenia and lumbar intervertebral disc degeneration in ovariectomized rats. Calcif. Tissue Int., 2004, 75: 205-213

[68]

Liu Q et al. Estrogen deficiency exacerbates intervertebral disc degeneration induced by spinal instability in rats. Spine, 2019, 44: E510-E519

[69]

Jin LY et al. Estradiol alleviates intervertebral disc degeneration through modulating the antioxidant enzymes and inhibiting autophagy in the model of menopause rats. Oxid. Med. Cell Longev., 2018, 2018: 7890291

[70]

Jia H et al. Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity. Sci. Rep., 2016, 6

[71]

Xiao ZF et al. Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice. Arthritis Res. Ther., 2018, 20: 207

[72]

Sheng B et al. Protective effect of estrogen against calcification in the cartilage endplate. Int. J. Clin. Exp. Pathol., 2018, 11: 1660-1666

[73]

Shelby, T. et al. The role of sex hormones in degenerative disc disease. Global Spine J, 21925682231152826 (2023).

[74]

Kupka J et al. Adrenoceptor expression during intervertebral disc degeneration. Int. J. Mol. Sci., 2020, 21: 2085

[75]

Wu T et al. Three-dimensional visualization and pathologic characteristics of cartilage and subchondral bone changes in the lumbar facet joint of an ovariectomized mouse model. Spine J., 2018, 18: 663-673

[76]

Gou Y et al. Salmon calcitonin attenuates degenerative changes in cartilage and subchondral bone in lumbar facet joint in an experimental rat model. Med. Sci. Monit., 2018, 24: 2849-2857

[77]

Chen H, Zhu H, Zhang K, Chen K, Yang H. Estrogen deficiency accelerates lumbar facet joints arthritis. Sci. Rep., 2017, 7

[78]

Zhao Y et al. Lumbar disk degeneration in female patients with and without ovariectomy: a case-control study. World Neurosurg., 2021, 156: 68-75

[79]

Ketut I. Suyasa*, I. G. N. Y. S. The role of aging, body mass index and estrogen on symptomatic lumbar osteoarthritis in post-menopausal women. Int. J. Res. Med. Sci., 2016, 4: 1325

[80]

Xu X et al. Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis. Med. Sci. Monit., 2019, 25: 3146-3153

[81]

Jiang A et al. Phenotype changes of subchondral plate osteoblasts based on a rat model of ovariectomy-induced osteoarthritis. Ann. Transl. Med., 2020, 8: 476

[82]

Høegh-Andersen P et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res. Ther., 2004, 6: R169-R180

[83]

Hashem G et al. Relaxin and beta-estradiol modulate targeted matrix degradation in specific synovial joint fibrocartilages: progesterone prevents matrix loss. Arthritis Res. Ther., 2006, 8: R98

[84]

Turner AS, Athanasiou KA, Zhu CF, Alvis MR, Bryant HU. Biochemical effects of estrogen on articular cartilage in ovariectomized sheep. Osteoarthr. Cartil., 1997, 5: 63-69

[85]

Dai G, Wang S, Li J, Liu C, Liu Q. The validity of osteoarthritis model induced by bilateral ovariectomy in guinea pig. J. Huazhong Univ. Sci. Technol. Med. Sci., 2006, 26: 716-719

[86]

Sniekers YH, Weinans H, Bierma-Zeinstra SM, van Leeuwen JP, van Osch GJ. Animal models for osteoarthritis: the effect of ovariectomy and estrogen treatment - a systematic approach. Osteoarthr. Cartil., 2008, 16: 533-541

[87]

Lu ZH, Zhang AH, Wang JC, Han KJ, Gao H. Estrogen alleviates post-traumatic osteoarthritis progression and decreases p-EGFR levels in female mouse cartilage. BMC Musculoskelet. Disord., 2022, 23

[88]

Srikanth VK et al. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthr. Cartil., 2005, 13: 769-781

[89]

Liu S et al. 17β-Estradiol inhibits intervertebral disc degeneration by down-regulating MMP-3 and MMP-13 and up-regulating type II collagen in a rat model. Artif. Cells Nanomed. Biotechnol., 2018, 46: 182-191

[90]

Wang H et al. 17β-Estradiol alleviates intervertebral disc degeneration by inhibiting NF-κB signal pathway. Life Sci., 2021, 284: 119874

[91]

Song XX, Jin LY, Li XF, Luo Y, Yu BW. Substance P Mediates Estrogen Modulation Proinflammatory Cytokines Release in Intervertebral Disc. Inflammation, 2020, 44: 506-517

[92]

Baron YM, Brincat MP, Galea R, Calleja N. Intervertebral disc height in treated and untreated overweight post-menopausal women. Hum. Reprod., 2005, 20: 3566-3570

[93]

Marty-Poumarat C, Scattin L, Marpeau M, Garreau De Loubresse C, Aegerter P. Natural history of progressive adult scoliosis. Spine, 2007, 32: 1227-1234

[94]

Marty-Poumarat C et al. Does hormone replacement therapy prevent lateral rotatory spondylolisthesis in postmenopausal women? Eur. Spine J., 2011, 21: 1127-1134

[95]

Muscat Baron Y, Brincat MP, Galea R, Calleja N. Low intervertebral disc height in postmenopausal women with osteoporotic vertebral fractures compared to hormone-treated and untreated postmenopausal women and premenopausal women without fractures. Climacteric, 2007, 10: 314-319

[96]

Park JH, Hong JY, Han K, Han SW, Chun EM. Relationship between hormone replacement therapy and spinal osteoarthritis: a nationwide health survey analysis of the elderly Korean population. BMJ Open, 2017, 7: e018063

[97]

Cheung P, Gossec L, Dougados M. What are the best markers for disease progression in osteoarthritis (OA)? Best. Pr. Res. Clin. Rheumatol., 2010, 24: 81-92

[98]

Yasuoka T, Nakashima M, Okuda T, Tatematsu N. Effect of estrogen replacement on temporomandibular joint remodeling in ovariectomized rats. J. Oral. Maxillofac. Surg., 2000, 58: 189-196

[99]

Abdrabuh A, Baljon K, Alyami Y. Impact of estrogen therapy on temporomandibular joints of rats: Histological and hormone analytical study. Saudi Dent. J., 2021, 33: 608-613

[100]

Torres-Chávez KE et al. Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Eur. J. Pain., 2011, 16: 204-216

[101]

Fischer L et al. The Influence of Sex and Ovarian Hormones on Temporomandibular Joint Nociception in Rats. J. Pain., 2008, 9: 630-638

[102]

Ham KD, Loeser RF, Lindgren BR, Carlson CS. Effects of long‐term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys. Arthritis Rheum., 2002, 46: 1956-1964

[103]

Schmidt IU, Wakley GK, Turner RT. Effects of Estrogen and Progesterone on Tibia Histomorphometry in Growing Rats. Calcif. Tissue Int., 2000, 67: 47-52

[104]

Chlebowski RT et al. Estrogen alone and joint symptoms in the Women’s Health Initiative randomized trial. Menopause, 2018, 25: 1313

[105]

Jung JH et al. Knee osteoarthritis and menopausal hormone therapy in postmenopausal women: a nationwide cross-sectional study. Menopause, 2018, 26: 598-602

[106]

Wluka AE, Davis SR, Bailey M, Stuckey S, Cicuttini F. Users of oestrogen replacement therapy have more knee cartilage than non-users. Ann. Rheum. Dis., 2001, 60: 332-336

[107]

Spector TD, Nandra D, Hart DJ, Doyle DV. Is hormone replacement therapy protective for hand and knee osteoarthritis in women?: The Chingford study. Ann. Rheum. Dis., 1997, 56: 432-434

[108]

Cirillo DJ, Wallace RB, Wu L, Yood RA. Effect of hormone therapy on risk of hip and knee joint replacement in the Women’s Health Initiative. Arthritis Rheum., 2006, 54: 3194-3204

[109]

Yang SD, Zhang F, Ma JT, Ding WY. Intervertebral disc ageing and degeneration: The antiapoptotic effect of oestrogen. Ageing Res. Rev., 2020, 57: 100978

[110]

Chen Q, Zhang W, Sadana N, Chen X. Estrogen receptors in pain modulation: cellular signaling. Biol. Sex. Differ., 2021, 12: 22

[111]

Sun LH et al. Estrogen modulation of visceral pain. J. Zhejiang Univ. Sci. B, 2019, 20: 628-636

[112]

Xunlu Y et al. Integrative bioinformatics analysis reveals potential gene biomarkers and analysis of function in human degenerative disc annulus fibrosus cells. Biomed. Res. Int., 2019, 2019: 9890279

[113]

Huang YC, Urban JP, Luk KD. Intervertebral disc regeneration: do nutrients lead the way? Nat. Rev. Rheumatol., 2014, 10: 561-566

[114]

Grunhagen TD, Shirazi-Adl A, Fairbank JC, Urban JP. Intervertebral disk nutrition: a review of factors influencing concentrations of nutrients and metabolites. Orthop. Clin. North Am., 2011, 42: 465-477

[115]

Stephan S, Johnson WE, Roberts S. The influence of nutrient supply and cell density on the growth and survival of intervertebral disc cells in 3D culture. Eur. Cell Mater., 2011, 22: 97-108

[116]

Adams MA, Dolan P, McNally DS. The internal mechanical functioning of intervertebral discs and articular cartilage, and its relevance to matrix biology. Matrix Biol., 2009, 28: 384-389

[117]

Zhang FAN, Zhao X, Shen H, Zhang C. Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int. J. Mol. Med., 2016, 37: 1439-1448

[118]

Zhou GQ, Yang F, Leung VVL, Cheung KMC. (v) Molecular and cellular biology of the intervertebral disc and the use of animal models. Curr. Orthop., 2008, 22: 267-273

[119]

Le Maitre CL, Freemont AJ, Hoyland JA. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res. Ther., 2007, 9: R45

[120]

Roberts S, Evans H, Trivedi J, Menage J. Histology and pathology of the human intervertebral disc. J. Bone Jt. Surg. Am., 2006, 88: 10-14

[121]

Kepler CKMDMBA, Ponnappan RKMD, Tannoury CAMD, Risbud MVP, Anderson DGMD. The molecular basis of intervertebral disc degeneration. Spine J., 2013, 13: 318-330

[122]

Xu YQ, Zhang ZH, Zheng YF, Feng SQ. Dysregulated miR-133a mediates loss of type ii collagen by directly targeting matrix metalloproteinase 9 (mmp9) in human intervertebral disc degeneration. Spine, 2016, 41: E717-E724

[123]

Zawilla NH et al. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration. J. Occup. Rehabil., 2013, 24: 370-381

[124]

Molinos M et al. Inflammation in intervertebral disc degeneration and regeneration. J. R. Soc. Interface, 2015, 12: 20150429

[125]

Lee S et al. Comparison of growth factor and cytokine expression in patients with degenerated disc disease and herniated nucleus pulposus. Clin. Biochem., 2009, 42: 1504-1511

[126]

Currò M et al. Differential expression of transglutaminase genes in patients with chronic periodontitis. Oral. Dis., 2014, 20: 616-623

[127]

Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res. Ther., 2005, 7: R732-R745

[128]

Johnson ZI, Schoepflin ZR, Choi H, Shapiro IM, Risbud MV. Disc in flames: Roles of TNF-alpha and IL-1beta in intervertebral disc degeneration. Eur. Cell Mater., 2015, 30: 104-117

[129]

Gu SX et al. MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc. Gene, 2015, 555: 80-87

[130]

Mavrogonatou E, Angelopoulou MT, Kletsas D. The catabolic effect of TNFα on bovine nucleus pulposus intervertebral disc cells and the restraining role of glucosamine sulfate in the TNFα-mediated up-regulation of MMP-3. J. Orthop. Res., 2014, 32: 1701-1707

[131]

Yao Z et al. Salubrinal Suppresses IL-17-Induced Upregulation of MMP-13 and Extracellular Matrix Degradation Through the NF-kB Pathway in Human Nucleus Pulposus Cells. Inflammation, 2016, 39: 1997-2007

[132]

Yang SD, Ma L, Yang DL, Ding WY. Combined effect of 17 beta-estradiol and resveratrol against apoptosis induced by interleukin-1 beta in rat nucleus pulposus cells via PI3K/Akt/caspase-3 pathway. PeerJ, 2016, 4: e1640

[133]

Song M et al. Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage. Biomed. Pharmacother., 2016, 84: 1137-1143

[134]

Yang SD et al. 17β-Estradiol protects against apoptosis induced by interleukin-1β in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13. Apoptosis, 2015, 20: 348-357

[135]

Gao XW, Su XT, Lu ZH, Ou J. 17β-Estradiol prevents extracellular matrix degradation by downregulating MMP3 expression via PI3K/Akt/FOXO3 pathway. Spine, 2020, 45: 292-299

[136]

Shen C, Yan J, Jiang LS, Dai LY. Autophagy in rat annulus fibrosus cells: evidence and possible implications. Arthritis Res. Ther., 2011, 13: R132

[137]

Yang D et al. 17β-Estradiol/extrogen receptor β alleviates apoptosis and enhances matrix biosynthesis of nucleus pulposus cells through regulating oxidative damage under a high glucose condition. Biomed. Pharmacother., 2018, 107: 1004-1009

[138]

Li P et al. 17beta-estradiol attenuates TNF-alpha-induced premature senescence of nucleus pulposus cells through regulating the ROS/NF-kappaB pathway. Int. J. Biol. Sci., 2017, 13: 145-156

[139]

Lin CY, Chen JH, Fu RH, Tsai CW. Induction of Pi form of glutathione S‑transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity. Chem. Res. Toxicol., 2014, 27: 1958-1966

[140]

Huang H, Zhong R, Xia Z, Song J, Feng L. Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways. Molecules, 2014, 19: 11196-11210

[141]

Kim DE, Kim B, Shin HS, Kwon HJ, Park ES. The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3β and ERK1/2 signaling pathway. Exp. Cell Res., 2014, 327: 264-275

[142]

Musumeci G et al. Post-traumatic caspase-3 expression in the adjacent areas of growth plate injury site: A morphological study. Int. J. Mol. Sci., 2013, 14: 15767-15784

[143]

Cravero JD et al. Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin‐like growth factor 1–mediated cell survival and proteoglycan synthesis. Arthritis Rheum., 2009, 60: 492-500

[144]

Guo F, Zou Y, Zheng Y. Moracin M inhibits lipopolysaccharide-induced inflammatory responses in nucleus pulposus cells via regulating PI3K/Akt/mTOR phosphorylation. Int. Immunopharmacol., 2018, 58: 80-86

[145]

Liu H et al. Protective role of 17β-estradiol on tumor necrosis factor-α-induced apoptosis in human nucleus pulposus cells. Mol. Med. Rep., 2017, 16: 1093-1100

[146]

Wang T et al. 17β-Estradiol inhibites tumor necrosis factor-α induced apoptosis of human nucleus pulposus cells via the PI3K/Akt pathway. Med. Sci. Monit., 2016, 22: 4312-4322

[147]

Guo HT et al. 17beta‑Estradiol protects against interleukin‑1beta‑induced apoptosis in rat nucleus pulposus cells via the mTOR/caspase‑3 pathway. Mol. Med. Rep., 2019, 20: 1523-1530

[148]

Kim J et al. Syringaresinol reverses age-related skin atrophy by suppressing FoxO3a-mediated matrix metalloproteinase–2 activation in Copper/Zinc superoxide dismutase–deficient mice. J. Investig. Dermatol., 2019, 139: 648-655

[149]

Li P et al. Osmolarity affects matrix synthesis in the nucleus pulposus associated with the involvement of MAPK pathways: A study of ex vivo disc organ culture system. J. Orthop. Res., 2016, 34: 1092-1100

[150]

Li P et al. Estrogen enhances matrix synthesis in nucleus pulposus cell through the estrogen receptor β-p38 MAPK pathway. Cell Physiol. Biochem., 2016, 39: 2216-2226

[151]

Lisowska B, Lisowski A, Siewruk K. Substance P and chronic pain in patients with chronic inflammation of connective tissue. PLoS One, 2015, 10: e0139206

[152]

Wu S et al. Occurrence of substance P and neurokinin receptors during the early phase of spinal fusion. Mol. Med. Rep., 2018, 17: 6691-6696

[153]

Zieglgansberger W. Substance P and pain chronicity. Cell Tissue Res., 2019, 375: 227-241

[154]

Zheng J et al. Reactive oxygen species mediate low back pain by upregulating substance P in intervertebral disc degeneration. Oxid. Med. Cell Longev., 2021, 2021: 6681815

[155]

Martinez AN, Philipp MT. Substance P and antagonists of the neurokinin-1 receptor in neuroinflammation associated with infectious and neurodegenerative diseases of the central nervous system. J. Neurol. Neuromed., 2016, 1: 29-36

[156]

Ho WZ, Douglas SD. Substance P and neurokinin-1 receptor modulation of HIV. J. Neuroimmunol., 2004, 157: 48-55

[157]

Bost KL. Tachykinin-mediated modulation of the immune response. Front. Biosci., 2004, 9: 3331-3332

[158]

Wang H et al. Different concentrations of 17β-estradiol modulates apoptosis induced by interleukin-1β in rat annulus fibrosus cells. Mol. Med. Rep., 2014, 10: 2745-2751

[159]

Zhao CM et al. 17β-Estradiol protects rat annulus fibrosus cells against apoptosis via α1 integrin-mediated adhesion to type I collagen: an in-vitro study. Med. Sci. Monit., 2016, 22: 1375-1383

[160]

Ni BB et al. The effect of transforming growth factor beta1 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation. Cytokine, 2014, 70: 87-96

[161]

Bai ZL et al. Toxic effects of levofloxacin on rat annulus fibrosus cells: an in-vitro study. Med. Sci. Monit., 2014, 20: 2205-2212

[162]

Wei HK et al. Levofloxacin increases apoptosis of rat annulus fibrosus cells via the mechanism of upregulating MMP-2 and MMP-13. Int. J. Clin. Exp. Med., 2015, 8: 20198-20207

[163]

Pang L, Yang K, Zhang Z. High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress. Biosci. Rep., 2020, 40: BSR20200262

[164]

Madiraju P, Gawri R, Wang H, Antoniou J, Mwale F. Mechanism of parathyroid hormone-mediated suppression of calcification markers in human intervertebral disc cells. Eur. Cell Mater., 2013, 25: 268-283

[165]

Yang SD et al. 17β-Estradiol protects against apoptosis induced by levofloxacin in rat nucleus pulposus cells by upregulating integrin α2β1. Apoptosis, 2014, 19: 789-800

[166]

Peng B, Li Y. Concerns about cell therapy for intervertebral disc degeneration. NPJ Regen. Med., 2022, 7: 46

[167]

Sheng B et al. Protective effect of estrogen against intervertebral disc degeneration is attenuated by miR-221 through targeting estrogen receptor α. Acta Biochim. Biophys. Sin., 2018, 50: 345-354

[168]

Han Y et al. Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-kappaB pathway: implications for disc degeneration. Biochem. Biophys. Res. Commun., 2019, 516: 1026-1032

[169]

Jiang Z et al. High glucose-induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells. J. Orthop. Res., 2018, 36: 2476-2483

[170]

Ding L et al. Effects of CCN3 on rat cartilage endplate chondrocytes cultured under serum deprivation in vitro. Mol. Med. Rep., 2016, 13: 2017-2022

[171]

Li D et al. Role of the mitochondrial pathway in serum deprivation-induced apoptosis of rat endplate cells. Biochem. Biophys. Res. Commun., 2014, 452: 354-360

[172]

Walsh DA et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology, 2010, 49: 1852-1861

[173]

Donell S. Subchondral bone remodelling in osteoarthritis. EFORT Open Rev., 2019, 4: 221-229

[174]

Yuan XL et al. Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies. Osteoarthr. Cartil., 2014, 22: 1077-1089

[175]

Grassel S, Zaucke F, Madry H. Osteoarthritis: novel molecular mechanisms increase our understanding of the disease pathology. J. Clin. Med., 2021, 10: 1938

[176]

Aso K et al. Time course and localization of nerve growth factor expression and sensory nerve growth during progression of knee osteoarthritis in rats. Osteoarthr. Cartil., 2022, 30: 1344-1355

[177]

Rockel JS, Kapoor M. Autophagy: controlling cell fate in rheumatic diseases. Nat. Rev. Rheumatol., 2017, 13: 193

[178]

Gwinn DM et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. cell, 2008, 30: 214-226

[179]

Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat. Rev. Rheumatol., 2015, 11: 35-44

[180]

Mei R et al. 17β-Estradiol induces mitophagy upregulation to protect chondrocytes via the SIRT1-mediated AMPK/mTOR signaling pathway. Front. Endocrinol. (Lausanne), 2021, 11: 615250

[181]

Matsuzaki T et al. Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann. Rheum. Dis., 2014, 73: 1397-1404

[182]

Zhang Z et al. Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1‐autophagy pathway. J. Cell Mol. Med., 2019, 23: 177-193

[183]

Montagnoli C et al. β-NGF and β-NGF receptor upregulation in blood and synovial fluid in osteoarthritis. Biol. Chem., 2017, 398: 1045-1054

[184]

Yu X et al. NGF increases FGF2 expression and promotes endothelial cell migration and tube formation through PI3K/Akt and ERK/MAPK pathways in human chondrocytes. Osteoarthr. Cartil., 2019, 27: 526-534

[185]

Huang JG et al. 17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway. Cell Mol. Biol. Lett., 2011, 16: 564-575

[186]

Shang X, Zhang L, Jin R, Yang H, Tao H. Estrogen regulation of the expression of pain factor NGF in rat chondrocytes. J. Pain. Res., 2021, 14: 931-940

[187]

Musgrave DS, Vogt MT, Nevitt MC, Cauley JA. Back problems among postmenopausal women taking estrogen replacement therapy: The study of osteoporotic fractures. Spine, 2001, 26: 1606-1612

[188]

Brynhildsen JO, Björs E, Skarsgård C, Hammar ML. Is hormone replacement therapy a risk factor for low back pain among postmenopausal women? Spine, 1998, 23: 809-813

[189]

Heuch I, Heuch I, Hagen K, Storheim K, Zwart JA. Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study. BMC Musculoskelet. Disord., 2023, 24

[190]

Ortmann O, Lattrich C. The treatment of climacteric symptoms. Dtsch Arztebl Int., 2012, 109: 316-323 quiz 324

[191]

Smith YR et al. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J. Neurosci., 2006, 26: 5777-5785

[192]

Hannan MT, Felson DT, Anderson JJ, Naimark A, Kannel WB. Estrogen use and radiographic osteoarthritis of the knee in women. The Framingham Osteoarthritis Study. Arthritis Rheum., 1990, 33: 525-532

[193]

Zhang Y et al. Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study. Arthritis Rheum., 1998, 41: 1867-1873

[194]

Kwan Tat S, Lajeunesse D, Pelletier JP, Martel-Pelletier J. Targeting subchondral bone for treating osteoarthritis: what is the evidence? Best. Pr. Res Clin. Rheumatol., 2010, 24: 51-70

[195]

Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat. Rev. Rheumatol., 2012, 8: 665-673

[196]

Kou XX et al. 17beta-estradiol aggravates temporomandibular joint inflammation through the NF-kappaB pathway in ovariectomized rats. Arthritis Rheum., 2011, 63: 1888-1897

[197]

Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA, 2002, 288: 321-333

[198]

Miller VM, Harman SM. An update on hormone therapy in postmenopausal women: mini-review for the basic scientist. Am. J. Physiol.-Heart C., 2017, 313: H1013-H1021

[199]

Canonico M et al. Hormone therapy and venous thromboembolism among postmenopausal women - Impact of the route of estrogen administration and progestogens: The ESTHER study. Circulation, 2007, 115: 840-845

[200]

Patel S, Homaei A, Raju AB, Meher BR. Estrogen: the necessary evil for human health, and ways to tame it. Biomed. Pharmacother., 2018, 102: 403-411

[201]

LaCroix AZ et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial EDITORIAL COMMENT. Obstet. Gynecol. Surv., 2011, 66: 427-429

[202]

Goldstein SR. Selective estrogen receptor modulators and bone health. Climacteric, 2022, 25: 56-59

[203]

Desmawati D, Sulastri D. Phytoestrogens and their health effect. Open Access Maced. J. Med Sci., 2019, 7: 495-499

[204]

Li X et al. The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc. Spine, 2008, 33: 2586-2595

[205]

Lewis JS, Jordan VC. Selective estrogen receptor modulators (SERMs): mechanisms of anticarcinogenesis and drug resistance. Mutat. Res., 2005, 591: 247-263

[206]

Lugo L, Villalvilla A, Largo R, Herrero-Beaumont G, Roman-Blas JA. Selective estrogen receptor modulators (SERMs): new alternatives for osteoarthritis? Maturitas, 2014, 77: 380-384

[207]

Downton T, Zhou F, Segara D, Jeselsohn R, Lim E. Oral selective estrogen receptor degraders (SERDs) in breast cancer: advances, challenges, and current status. Drug Des. Devel. Ther., 2022, 16: 2933-2948

[208]

Deng Y, Li L, Li C, Wang F, Qu Y. Efficacy of combined medication of risedronate sodium and selective estrogen receptor modulator on the postmenopausal osteoporosis. Pak. J. Pharm. Sci., 2020, 33: 495-498

[209]

Wilcox NS et al. Sex-specific cardiovascular risks of cancer and its therapies. Circ. Res., 2022, 130: 632-651

[210]

Bhadouria N, Berman AG, Wallace JM, Holguin N. Raloxifene stimulates estrogen signaling to protect against age- and sex-related intervertebral disc degeneration in mice. Front. Bioeng. Biotechnol., 2022, 10: 924918

[211]

Chen MN, Lin CC, Liu CF. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric, 2015, 18: 260-269

[212]

Lagari VS, Levis S. Phytoestrogens and bone health. Curr. Opin. Endocrinol. Diabetes Obes., 2010, 17: 546-553

[213]

Chudzinska M et al. Resveratrol and cardiovascular system-the unfulfilled hopes. Ir. J. Med Sci., 2021, 190: 981-986

[214]

Gilmer G et al. Uncovering the “riddle of femininity” in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment. Osteoarthr. Cartil., 2023, 31: 447-457

[215]

Kyllönen ES, Väänänen HK, Vanharanta JHV, Heikkinen JE. Influence of estrogen-progestin treatment on back pain and disability among slim premenopausal women with low lumbar spine bone mineral density: A 2-year placebo-controlled randomized trial. Spine (Philos. Pa 1976), 1999, 24: 704-708

[216]

Yang JH, Kim JH, Lim DS, Oh KJ. Effect of combined sex hormone replacement on bone/cartilage turnover in a murine model of osteoarthritis. Clin. Orthop. Surg., 2012, 4: 234-241

Funding

Australian Centre for HIV and Hepatitis Virology Research (ACH2)

China Scholarship Council (CSC)

Department of Health | National Health and Medical Research Council (NHMRC)

National Natural Science Foundation of China (National Science Foundation of China)

Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation)

Assistant Secretary of Defense for Health Affairs endorsed by the US Department of Defense (award no. W81XWH2010909)

AI Summary AI Mindmap
PDF

137

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/